Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription.
Cell Rep
; 37(2): 109803, 2021 10 12.
Article
en En
| MEDLINE
| ID: mdl-34644581
ABSTRACT
Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in the pediatric, elderly, and immunocompromised individuals. RSV non-structural protein NS1 is a known cytosolic immune antagonist, but how NS1 modulates host responses remains poorly defined. Here, we observe NS1 partitioning into the nucleus of RSV-infected cells, including the human airway epithelium. Nuclear NS1 coimmunoprecipitates with Mediator complex and is chromatin associated. Chromatin-immunoprecipitation demonstrates enrichment of NS1 that overlaps Mediator and transcription factor binding within the promoters and enhancers of differentially expressed genes during RSV infection. Mutation of the NS1 C-terminal helix reduces NS1 impact on host gene expression. These data suggest that nuclear NS1 alters host responses to RSV infection by binding at regulatory elements of immune response genes and modulating host gene transcription. Our study identifies another layer of regulation by virally encoded proteins that shapes host response and impacts immunity to RSV.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Transcripción Genética
/
Células Dendríticas
/
Cromatina
/
Núcleo Celular
/
Proteínas no Estructurales Virales
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Virus Sincitial Respiratorio Humano
/
Infecciones por Virus Sincitial Respiratorio
/
Células Epiteliales
/
Pulmón
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos